Behavioral or Solifenacin Therapy for Urinary Symptoms in Parkinson Disease

行为疗法或索利那新疗法治疗帕金森病泌尿系统症状

• 批准号: 10063075
• 负责人: Elizabeth Camille Vaughan
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063075
• 关键词: Address; Adult; Age; Anti-Cholinergics; Antiparkinson Agents; Area; Behavior Therapy; Behavioral; Benchmarking; Bladder; Bladder Control; Bradykinesia; Brain; CNS processing; Caregiver Burden; Caring; Clinical; Cognitive; Consultations; Disease; Equilibrium; Evaluation; Exercise; Exercise Therapy; Frequencies; Functional Imaging; Future; Gender; General Population; Glare; Goals; Health; Healthcare; Impaired cognition; Impairment; Incontinence; Individual; Institutionalization; International; Intervention; Lead; Learning; Measures; Modeling; Motor Skills; Muscle Contraction; Nervous System control; Neuraxis; Neurodegenerative Disorders; Neuronal Plasticity; Neuropsychology; Nocturia; Outcome; Outcome Measure; Overactive Bladder; Parkinson Disease; Participant; Patients; Pelvic Floor Muscle; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physical Function; Physical Medicine; Population; Prevalence; Questionnaires; Randomized; Randomized Controlled Trials; Rehabilitation therapy; Research; Risk Factors; Severities; Signal Transduction; Site; Spouse Caregiver; Structure; Symptoms; Time; Training; Tremor; United States; Urge Incontinence; Urinary Incontinence; Veterans; Voice; Woman; afferent nerve; associated symptom; base; behavioral study; burden of illness; cognitive function; common symptom; comparative effectiveness; compare effectiveness; design; disability; evidence base; executive function; falls; improved; men; micturition urgency; mortality; motor disorder; motor skill learning; motor symptom; neuromechanism; non-motor symptom; novel strategies; patient safety; primary outcome; reduce symptoms; research and development; response; sensory input; treatment guidelines; treatment optimization; treatment response; urinary

The number of persons with Parkinson Disease (PD) in the United States is expected to double by 2030 as the population ages. Importantly, this increase in the prevalence of PD will have greater impact within the Department of Veterans Affairs (VA) because the Veteran population is older than the general population and Veterans with PD are more likely than those without PD to rely solely on VA for their health care. While PD is often characterized by the motor symptoms of the disease (tremor, bradykinesia, rigidity), non-motor symptoms such as urinary symptoms correlate more closely with impaired well-being as the disease progresses. However, the impact of urinary symptoms in PD extends beyond worsened well-being. The urinary symptoms of overactive bladder (OAB), including urgency, frequency, and nocturia, with or without urinary incontinence, are the most common urinary symptoms of PD. OAB symptoms are associated with falls (a cause of increased mortality in PD), with spouse/caregiver stress, and, ultimately with institutionalization, thus it is critical that we optimize the care of urinary symptoms for Veterans with PD. Several studies suggest abnormal central nervous system processing of sensory input from bladder afferent nerves contributes to OAB symptoms in PD, possibly because of delayed recognition of bladder fullness. This mirrors findings in non-PD populations with OAB. In the non-PD OAB population, pelvic floor muscle contractions diminish bladder muscle contraction and recent evidence demonstrates that behavioral training with pelvic floor muscle exercises improves the cortical integration of bladder afferent signals. Pelvic floor muscle exercise-based behavioral therapy for OAB symptoms requires individuals to learn a motor skill and implement an adaptive behavioral strategy to delay the need to void. Because of its effectiveness compared to drug therapy, pelvic floor muscle exercise-based behavioral therapy is recommended first-line in men and women with OAB who do not have PD. However, the most recent clinical guidelines for the treatment of urinary symptoms in PD recommend treatment with anticholinergic drugs. While some anticholinergic drugs are effective in reducing symptoms of OAB, it is important to note that there is a glaring lack of an empirical evidence base to promote these drugs in the setting of PD given that they add to the anticholinergic burden of antiparkinsonian therapy, and may worsen the cognitive and autonomic burdens of the illness. Therefore, randomized controlled trials (RCTs) are needed to optimize treatment paradigms for urinary symptoms in PD. We propose a three-site, RCT conducted at the Atlanta (lead site), Birmingham and Richmond VA's to establish non-inferiority of pelvic floor muscle exercise-based behavioral therapy compared to drug therapy for OAB symptoms in adults with PD. Groups will be stratified by OAB symptom severity, PD motor symptom severity, gender, and site. We will randomize 90 participants in order to complete the study in 80 participants, assuming 85% power and a non-inferiority margin for the OAB symptom score of 15% at 12-weeks. The primary outcome measure will be urinary symptom severity as measured by the International Consultation on Incontinence Questionnaire(ICIQ)-OAB symptom score collected at 3 time points during the study: baseline, 6 weeks, and 12 weeks. Our benchmark for successful treatment will be a ≥ 2 point reduction in the ICIQ-OAB symptom score, which corresponds with perceived benefit in preliminary studies of behavioral therapy treatment for OAB symptoms in PD. To evaluate the primary efficacy outcome, we will utilize a random effects mixed model and adjust for baseline OAB symptom score severity. Additionally, in order to better understand central control mechanisms of bladder function, we will determine if domain-specific cognitive function impacts the response to exercise-based behavioral therapy or drug therapy for urinary symptoms. At baseline and 12 weeks, randomized participants will undergo a brief neuropsychological battery. Understanding how domain- specific cognitive function impacts response to treatment may inform new targets for rehabilitation therapy.

帕金森氏病（PD）的人数预计到2030年将翻一番 人口年龄。重要的是，PD患病率的增加将在 退伍军人事务部（VA）是因为退伍军人人口比一般人口大， 具有PD的退伍军人比没有PD的退伍军人仅依靠VA来进行医疗保健。而PD是 通常以疾病的运动症状（震颤，胸肌，僵化），非运动症状为特征 例如尿症状与随着疾病的进展，与幸福感更紧密相关。 但是，PD中尿症状的影响范围超出了恶化的福祉。尿症状 过度活跃的膀胱（OAB），包括紧迫性，频率和夜尿，有或没有尿失禁， 是PD最常见的尿症状。 OAB症状与跌倒有关（原因 PD的死亡率提高），配偶/照顾者的压力以及最终的制度化，因此是 至关重要的是，我们优化具有PD的退伍军人的尿符号的护理。 几项研究表明，中枢神经系统对膀胱的感觉输入的异常 传入神经有助于PD中的OAB症状，这可能是由于膀胱的识别延迟 丰满。这反映了与OAB的非PD种群中的发现。在非PD OAB种群中，骨盆底 肌肉收缩减少膀胱肌肉收缩，最近的证据表明行为 用骨盆底肌肉运动训练可以改善膀胱传入信号的皮质整合。骨盆 基于OAB症状的基于肌肉运动的行为疗法要求个人学习运动技能 并实施一种自适应行为策略，以延迟无效的需求。由于其有效性 与药物治疗相比，建议在 没有PD的OAB的男性和女人。但是，治疗的最新临床指南 PD建议治疗抗胆碱能药物的尿症状。而一些抗胆碱能药物 有效地减少OAB症状，重要的是要注意，缺乏经验 鉴于它们增加 Antiparkinsonian疗法，可能会担心该疾病的认知和自主性伯恩斯。所以， 需要随机对照试验（RCT）来优化PD中尿症状的治疗范例。 我们建议在亚特兰大（领先地点），伯明翰和里士满弗吉尼亚州的三站 与药物治疗相比 PD成人的OAB症状。组将通过OAB症状严重程度，PD运动症状进行分层 严重性，性别和场地。我们将随机分配90名参与者，以完成80名参与者的研究， 假设在12周的OAB症状得分为15％的OAB症状得分的功率为85％。这 主要结局指标将是通过国际咨询衡量的尿症状严重程度 尿失禁问卷（ICIQ）-OAB症状评分在研究过程中以3个时间点收集：基线，6 几周和12周。我们成功治疗的基准将降低ICIQ-OAB≥2点 症状评分与行为疗法的初步研究相对应 PD中OAB症状的治疗。为了评估主要效率结果，我们将利用随机效应 混合模型并调整基线OAB症状评分严重程度。此外，为了更好地理解 膀胱功能的中央控制机制，我们将确定域特异性认知功能是否影响 对基于运动的行为疗法或药物治疗的反应。基线和12 几周，随机参与者将经历短暂的神经心理电池。了解领域如何 特定的认知功能影响对治疗的反应可能为康复治疗的新靶标提供依据。